, Volume 40, Issue 2 Supplement, pp S2-S17

The insulin signalling system and the IRS proteins


During the past few years, the insulin signalling system has emerged as a flexible network of interacting proteins. By utilizing the insulin receptor substrate (IRS)-proteins (IRS-1 and IRS-2), the insulin signal can be amplified or attenuated independently of insulin binding and tyrosine kinase activity, providing an extensible mechanism for signal transmission in multiple cellular backgrounds. By employing IRS-proteins to engage various signalling proteins, the insulin receptor avoids the stoichiometric constraints encountered by receptors which directly recruit SH2-proteins to their autophosphorylation sites. Finally, the shared use of IRS-proteins by multiple receptors is likely to reveal important connections between insulin and other hormones and cytokines which were previously unrecognized, or observed but unexplained. [Diabetologia (1997) 40: S 2–S 17]